FI113271B - Taksaanijohdannaisten fosfono-oksimetyylieetterit - Google Patents
Taksaanijohdannaisten fosfono-oksimetyylieetterit Download PDFInfo
- Publication number
- FI113271B FI113271B FI943749A FI943749A FI113271B FI 113271 B FI113271 B FI 113271B FI 943749 A FI943749 A FI 943749A FI 943749 A FI943749 A FI 943749A FI 113271 B FI113271 B FI 113271B
- Authority
- FI
- Finland
- Prior art keywords
- hydroxy
- mmol
- paclitaxel
- hydrogen
- formula
- Prior art date
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- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 title claims abstract description 64
- VBKBIDUVUIYPEC-UHFFFAOYSA-N phosphonooxymethoxymethyl dihydrogen phosphate Chemical class OP(O)(=O)OCOCOP(O)(O)=O VBKBIDUVUIYPEC-UHFFFAOYSA-N 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 242
- 229960001592 paclitaxel Drugs 0.000 claims description 239
- 229910052739 hydrogen Inorganic materials 0.000 claims description 219
- 229930012538 Paclitaxel Natural products 0.000 claims description 174
- -1 3-amino-2-hydroxypropanoyloxy group Chemical group 0.000 claims description 169
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 156
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 134
- 238000002360 preparation method Methods 0.000 claims description 113
- 238000000034 method Methods 0.000 claims description 108
- 239000001257 hydrogen Substances 0.000 claims description 104
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 49
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 47
- 125000006239 protecting group Chemical group 0.000 claims description 43
- 229940123237 Taxane Drugs 0.000 claims description 36
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 32
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 30
- 230000008569 process Effects 0.000 claims description 25
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 125000004423 acyloxy group Chemical group 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 229910052751 metal Inorganic materials 0.000 claims description 15
- 239000002184 metal Substances 0.000 claims description 15
- 125000004043 oxo group Chemical group O=* 0.000 claims description 15
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 10
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 10
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 9
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 7
- 150000004703 alkoxides Chemical class 0.000 claims description 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 125000006257 n-butyloxycarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])OC(*)=O 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 12
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 101150093595 ACO1 gene Proteins 0.000 claims 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 230000000259 anti-tumor effect Effects 0.000 abstract description 12
- 239000002246 antineoplastic agent Substances 0.000 abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 747
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 287
- 239000000243 solution Substances 0.000 description 262
- 235000019439 ethyl acetate Nutrition 0.000 description 257
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 184
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 139
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 135
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 111
- 239000000047 product Substances 0.000 description 101
- 239000011541 reaction mixture Substances 0.000 description 89
- 239000000203 mixture Substances 0.000 description 87
- 238000005481 NMR spectroscopy Methods 0.000 description 83
- 238000006243 chemical reaction Methods 0.000 description 78
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 75
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 73
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 71
- 239000012267 brine Substances 0.000 description 69
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 69
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 68
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 64
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 61
- 239000007787 solid Substances 0.000 description 61
- 239000000741 silica gel Substances 0.000 description 60
- 229910002027 silica gel Inorganic materials 0.000 description 60
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 59
- 239000011734 sodium Substances 0.000 description 55
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 239000000706 filtrate Substances 0.000 description 43
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 42
- OVMSOCFBDVBLFW-VHLOTGQHSA-N (-)-Baccatin III Natural products O([C@@H]1[C@@]2(C[C@H](O)C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)O)C(=O)C1=CC=CC=C1 OVMSOCFBDVBLFW-VHLOTGQHSA-N 0.000 description 41
- 238000004128 high performance liquid chromatography Methods 0.000 description 40
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- 229920006395 saturated elastomer Polymers 0.000 description 38
- 238000003756 stirring Methods 0.000 description 38
- 239000002904 solvent Substances 0.000 description 37
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 36
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 36
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 34
- 229910052786 argon Inorganic materials 0.000 description 34
- 238000004809 thin layer chromatography Methods 0.000 description 33
- 238000003818 flash chromatography Methods 0.000 description 30
- 150000003839 salts Chemical class 0.000 description 30
- 239000003921 oil Substances 0.000 description 29
- 235000019198 oils Nutrition 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 27
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 27
- 239000006260 foam Substances 0.000 description 26
- 235000017557 sodium bicarbonate Nutrition 0.000 description 26
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 26
- 239000007858 starting material Substances 0.000 description 26
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
- 206010028980 Neoplasm Diseases 0.000 description 25
- 238000005160 1H NMR spectroscopy Methods 0.000 description 24
- 238000004458 analytical method Methods 0.000 description 24
- 229930014667 baccatin III Natural products 0.000 description 23
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical compound O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 22
- 239000000460 chlorine Substances 0.000 description 22
- 239000012044 organic layer Substances 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- 239000000725 suspension Substances 0.000 description 21
- 241000699670 Mus sp. Species 0.000 description 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 229910052938 sodium sulfate Inorganic materials 0.000 description 20
- 235000011152 sodium sulphate Nutrition 0.000 description 20
- 239000004342 Benzoyl peroxide Substances 0.000 description 19
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 19
- 235000019400 benzoyl peroxide Nutrition 0.000 description 19
- 238000010898 silica gel chromatography Methods 0.000 description 18
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 17
- 239000010410 layer Substances 0.000 description 17
- 229910052708 sodium Inorganic materials 0.000 description 17
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 16
- 239000002253 acid Substances 0.000 description 16
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 16
- HDFFVHSMHLDSLO-UHFFFAOYSA-M dibenzyl phosphate Chemical class C=1C=CC=CC=1COP(=O)([O-])OCC1=CC=CC=C1 HDFFVHSMHLDSLO-UHFFFAOYSA-M 0.000 description 16
- 238000010265 fast atom bombardment Methods 0.000 description 16
- 238000001914 filtration Methods 0.000 description 16
- CPZBTYRIGVOOMI-UHFFFAOYSA-N methylsulfanyl(methylsulfanylmethoxy)methane Chemical compound CSCOCSC CPZBTYRIGVOOMI-UHFFFAOYSA-N 0.000 description 16
- 239000012074 organic phase Substances 0.000 description 16
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 15
- 238000004949 mass spectrometry Methods 0.000 description 15
- 239000002808 molecular sieve Substances 0.000 description 15
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 15
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 14
- 239000002585 base Substances 0.000 description 14
- 229910052717 sulfur Inorganic materials 0.000 description 14
- 229960004418 trolamine Drugs 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 13
- 229910052799 carbon Inorganic materials 0.000 description 13
- 208000025033 X-linked centronuclear myopathy Diseases 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 12
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 12
- 235000009518 sodium iodide Nutrition 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 125000000304 alkynyl group Chemical group 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 11
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 11
- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 125000003342 alkenyl group Chemical group 0.000 description 10
- 239000012298 atmosphere Substances 0.000 description 10
- 238000005859 coupling reaction Methods 0.000 description 10
- 238000007872 degassing Methods 0.000 description 10
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 10
- 238000004896 high resolution mass spectrometry Methods 0.000 description 10
- 238000005984 hydrogenation reaction Methods 0.000 description 10
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 10
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 10
- 235000019345 sodium thiosulphate Nutrition 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 9
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 9
- 235000019270 ammonium chloride Nutrition 0.000 description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 229910052744 lithium Inorganic materials 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 229910052763 palladium Inorganic materials 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 229940001474 sodium thiosulfate Drugs 0.000 description 9
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 8
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 230000003197 catalytic effect Effects 0.000 description 8
- 230000008878 coupling Effects 0.000 description 8
- 238000010168 coupling process Methods 0.000 description 8
- 238000000921 elemental analysis Methods 0.000 description 8
- 238000002513 implantation Methods 0.000 description 8
- 239000004475 Arginine Substances 0.000 description 7
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 7
- 125000004104 aryloxy group Chemical group 0.000 description 7
- 239000011575 calcium Substances 0.000 description 7
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 239000011521 glass Substances 0.000 description 7
- ZSSFPSNLAUYOFG-UHFFFAOYSA-N methylsulfanylmethanol Chemical compound CSCO ZSSFPSNLAUYOFG-UHFFFAOYSA-N 0.000 description 7
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 7
- 238000010926 purge Methods 0.000 description 7
- 239000002002 slurry Substances 0.000 description 7
- 159000000000 sodium salts Chemical class 0.000 description 7
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 6
- 239000004472 Lysine Substances 0.000 description 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 150000001721 carbon Chemical group 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/6551—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a four-membered ring
- C07F9/65512—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a four-membered ring condensed with carbocyclic rings or carbocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
- H01L21/00—Processes or apparatus adapted for the manufacture or treatment of semiconductor or solid state devices or of parts thereof
- H01L21/02—Manufacture or treatment of semiconductor devices or of parts thereof
- H01L21/04—Manufacture or treatment of semiconductor devices or of parts thereof the devices having potential barriers, e.g. a PN junction, depletion layer or carrier concentration layer
- H01L21/48—Manufacture or treatment of parts, e.g. containers, prior to assembly of the devices, using processes not provided for in a single one of the subgroups H01L21/06 - H01L21/326
- H01L21/4814—Conductive parts
- H01L21/4821—Flat leads, e.g. lead frames with or without insulating supports
- H01L21/4839—Assembly of a flat lead with an insulating support, e.g. for TAB
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Biochemistry (AREA)
- Manufacturing & Machinery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- General Physics & Mathematics (AREA)
- General Chemical & Material Sciences (AREA)
- Computer Hardware Design (AREA)
- Epidemiology (AREA)
- Power Engineering (AREA)
- Microelectronics & Electronic Packaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epoxy Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10801593A | 1993-08-17 | 1993-08-17 | |
US10801593 | 1993-08-17 | ||
US15484093A | 1993-11-24 | 1993-11-24 | |
US15484093 | 1993-11-24 | ||
US24511994A | 1994-05-17 | 1994-05-17 | |
US24511994 | 1994-05-17 |
Publications (3)
Publication Number | Publication Date |
---|---|
FI943749A0 FI943749A0 (fi) | 1994-08-15 |
FI943749A FI943749A (fi) | 1995-02-18 |
FI113271B true FI113271B (fi) | 2004-03-31 |
Family
ID=27380403
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI943749A FI113271B (fi) | 1993-08-17 | 1994-08-15 | Taksaanijohdannaisten fosfono-oksimetyylieetterit |
Country Status (20)
Country | Link |
---|---|
EP (1) | EP0639577B1 (hu) |
JP (1) | JP3062986B2 (hu) |
KR (1) | KR100249306B1 (hu) |
CN (2) | CN1051315C (hu) |
AT (1) | ATE217629T1 (hu) |
AU (2) | AU694941B2 (hu) |
CA (1) | CA2129288C (hu) |
CY (1) | CY2295B1 (hu) |
CZ (1) | CZ194794A3 (hu) |
DE (1) | DE69430611T2 (hu) |
DK (1) | DK0639577T3 (hu) |
ES (1) | ES2176212T3 (hu) |
FI (1) | FI113271B (hu) |
HU (1) | HUT67742A (hu) |
IL (2) | IL110660A0 (hu) |
NO (1) | NO309093B1 (hu) |
NZ (1) | NZ264240A (hu) |
PL (1) | PL179636B1 (hu) |
PT (1) | PT639577E (hu) |
RU (1) | RU2128661C1 (hu) |
Families Citing this family (46)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6515009B1 (en) | 1991-09-27 | 2003-02-04 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US5811447A (en) | 1993-01-28 | 1998-09-22 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
FR2698871B1 (fr) | 1992-12-09 | 1995-02-24 | Rhone Poulenc Rorer Sa | Nouveau taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent. |
CA2111527C (en) * | 1992-12-24 | 2000-07-18 | Jerzy Golik | Phosphonooxymethyl ethers of taxane derivatives |
US5981568A (en) | 1993-01-28 | 1999-11-09 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US6491938B2 (en) | 1993-05-13 | 2002-12-10 | Neorx Corporation | Therapeutic inhibitor of vascular smooth muscle cells |
US6593482B2 (en) | 1993-02-01 | 2003-07-15 | Aventis Pharma S.A. | Methods for preparing new taxoids and pharmaceutical compositions containing them |
FR2732340B1 (fr) * | 1995-03-27 | 1997-04-30 | Rhone Poulenc Rorer Sa | Nouveaux taxoides, leur preparation et les compositions pharmaceutiques qui les contiennent |
US6040466A (en) * | 1996-03-25 | 2000-03-21 | Rhone Poulenc Rorer Sa | Taxoids, their preparation and pharmaceutical compositions containing them |
US6232477B1 (en) | 1996-03-25 | 2001-05-15 | Aventis Pharma S.A. | Methods of preparing new taxoids and pharmaceutical compositions containing them |
US5677470A (en) * | 1994-06-28 | 1997-10-14 | Tanabe Seiyaku Co., Ltd. | Baccatin derivatives and processes for preparing the same |
US6458976B1 (en) | 1994-10-28 | 2002-10-01 | The Research Foundation Of State University Of New York | Taxoid anti-tumor agents, pharmaceutical compositions, and treatment methods |
US6500858B2 (en) | 1994-10-28 | 2002-12-31 | The Research Foundation Of The State University Of New York | Taxoid anti-tumor agents and pharmaceutical compositions thereof |
AU4133096A (en) * | 1994-10-28 | 1996-05-23 | Research Foundation Of The State University Of New York, The | Taxoid derivatives, their preparation and their use as antitumor agents |
CA2162759A1 (en) * | 1994-11-17 | 1996-05-18 | Kenji Tsujihara | Baccatin derivatives and processes for preparing the same |
US6372780B2 (en) | 1995-03-27 | 2002-04-16 | Aventis Pharma S.A. | Methods of treating cell lines expressing multidrug resistance P-glycoprotein |
MA23823A1 (fr) * | 1995-03-27 | 1996-10-01 | Aventis Pharma Sa | Nouveaux taxoides, leur preparation et les compositions qui les contiennent |
US5847170A (en) * | 1995-03-27 | 1998-12-08 | Rhone-Poulenc Rorer, S.A. | Taxoids, their preparation and pharmaceutical compositions containing them |
TW354293B (en) * | 1995-06-06 | 1999-03-11 | Bristol Myers Squibb Co | Prodrugs of paclitaxel derivatives |
US6245805B1 (en) * | 1995-10-26 | 2001-06-12 | Baker Norton Pharmaceuticals, Inc. | Method, compositions and kits for increasing the oral bioavailability of pharmaceutical agents |
EP0822815A4 (en) * | 1996-01-31 | 1998-04-01 | Bristol Myers Squibb Co | PROCESS FOR MAKING ORAL-LIKE TAXANES ACTIVE FROM THE PHARMACEUTICAL VIEW |
JP2001521503A (ja) | 1997-03-31 | 2001-11-06 | ネオルックス コーポレイション | 血管平滑筋細胞の治療的阻害物質 |
US6156789A (en) * | 1998-03-17 | 2000-12-05 | Rhone-Poulenc Rorer S.A. | Method for treating abnormal cell proliferation in the brain |
US6204257B1 (en) * | 1998-08-07 | 2001-03-20 | Universtiy Of Kansas | Water soluble prodrugs of hindered alcohols |
EP1020188A1 (en) * | 1999-01-13 | 2000-07-19 | Aventis Pharma S.A. | New use of taxoid derivatives |
US6362172B2 (en) * | 2000-01-20 | 2002-03-26 | Bristol-Myers Squibb Company | Water soluble prodrugs of azole compounds |
PL350315A1 (en) | 2000-02-02 | 2002-12-02 | Univ Florida State Res Found | C7 carbonate substituted taxanes as antitumor agents |
US6649632B2 (en) | 2000-02-02 | 2003-11-18 | Fsu Research Foundation, Inc. | C10 ester substituted taxanes |
CA2368151A1 (en) | 2000-02-02 | 2001-08-09 | Florida State University Research Foundation, Inc. | C10 carbonate substituted taxanes as antitumor agents |
DE60131537T2 (de) | 2000-06-22 | 2008-10-23 | Nitromed, Inc., Lexington | Nitrosierte und nitrosylierte taxane, zubereitungen und methoden der verwendung |
US6448401B1 (en) | 2000-11-20 | 2002-09-10 | Bristol-Myers Squibb Company | Process for water soluble azole compounds |
EP1497275A4 (en) * | 2002-04-05 | 2006-04-12 | Natural Pharmaceuticals Inc | SELECTIVE ACYLATION OF SECONDARY HYDROXYL GROUPS |
EP1534674A4 (en) | 2002-08-02 | 2007-11-28 | Immunogen Inc | CYTOTOXIC AGENTS CONTAINING NEW, EFFECTIVE TAXANES AND THEIR THERAPEUTIC USE |
US7390898B2 (en) * | 2002-08-02 | 2008-06-24 | Immunogen Inc. | Cytotoxic agents containing novel potent taxanes and their therapeutic use |
US8703982B2 (en) | 2003-03-17 | 2014-04-22 | Phyton Holdings Llc | Purification of taxanes |
HN2005000054A (es) | 2004-02-13 | 2009-02-18 | Florida State University Foundation Inc | Taxanos sustituidos con esteres de ciclopentilo en c10 |
JP2011517455A (ja) | 2008-03-31 | 2011-06-09 | フロリダ・ステイト・ユニバーシティ・リサーチ・ファウンデイション・インコーポレイテッド | C(10)エチルエステルおよびc(10)シクロプロピルエステル置換タキサン |
EP2896632B1 (en) | 2009-11-13 | 2017-10-25 | Daiichi Sankyo Europe GmbH | Material and methods for treating or preventing HER-3 associated diseases |
CA2815154A1 (en) | 2010-08-06 | 2012-02-09 | U3 Pharma Gmbh | Use of her3 binding agents in prostate treatment |
BR112014004313A8 (pt) | 2011-08-25 | 2023-02-07 | Bonac Corp | Composto glicosídeo, métodos de produção de um tioéter, de éter e de composto glicosídeo, e, éter. |
CN104650012A (zh) | 2013-11-22 | 2015-05-27 | 天士力控股集团有限公司 | 一种紫杉烷类化合物 |
WO2016159374A1 (ja) * | 2015-04-02 | 2016-10-06 | 株式会社ボナック | 配糖体化合物の製造方法 |
CN110862410A (zh) * | 2018-08-27 | 2020-03-06 | 深圳福山生物科技有限公司 | 三氟甲基硒化合物及其用途 |
US11976035B2 (en) | 2019-06-12 | 2024-05-07 | Nouryon Chemicals International B.V. | Process for the production of diacyl peroxides |
WO2020249691A1 (en) | 2019-06-12 | 2020-12-17 | Nouryon Chemicals International B.V. | Process for the production of diacyl peroxides |
ES2963356T3 (es) * | 2019-06-12 | 2024-03-26 | Nouryon Chemicals Int Bv | Método para aislar ácido carboxílico a partir de una corriente lateral acuosa |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2678930B1 (fr) * | 1991-07-10 | 1995-01-13 | Rhone Poulenc Rorer Sa | Procede de preparation de derives de la baccatine iii et de la desacetyl-10 baccatine iii. |
FR2679230B1 (fr) * | 1991-07-16 | 1993-11-19 | Rhone Poulenc Rorer Sa | Nouveaux derives d'analogues du taxol, leur preparation et les compositions qui les contiennent. |
US5229526A (en) * | 1991-09-23 | 1993-07-20 | Florida State University | Metal alkoxides |
US5272171A (en) * | 1992-02-13 | 1993-12-21 | Bristol-Myers Squibb Company | Phosphonooxy and carbonate derivatives of taxol |
CA2111527C (en) * | 1992-12-24 | 2000-07-18 | Jerzy Golik | Phosphonooxymethyl ethers of taxane derivatives |
-
1994
- 1994-08-02 CA CA002129288A patent/CA2129288C/en not_active Expired - Fee Related
- 1994-08-11 CZ CZ941947A patent/CZ194794A3/cs unknown
- 1994-08-12 JP JP6250219A patent/JP3062986B2/ja not_active Expired - Fee Related
- 1994-08-12 HU HU9402342A patent/HUT67742A/hu active IP Right Revival
- 1994-08-15 IL IL11066094A patent/IL110660A0/xx unknown
- 1994-08-15 NZ NZ264240A patent/NZ264240A/en unknown
- 1994-08-15 NO NO943002A patent/NO309093B1/no unknown
- 1994-08-15 FI FI943749A patent/FI113271B/fi not_active IP Right Cessation
- 1994-08-15 RU RU94029662A patent/RU2128661C1/ru not_active IP Right Cessation
- 1994-08-15 CN CN94109468A patent/CN1051315C/zh not_active Expired - Fee Related
- 1994-08-15 AU AU70267/94A patent/AU694941B2/en not_active Ceased
- 1994-08-16 KR KR1019940020177A patent/KR100249306B1/ko not_active IP Right Cessation
- 1994-08-16 AT AT94112803T patent/ATE217629T1/de not_active IP Right Cessation
- 1994-08-16 ES ES94112803T patent/ES2176212T3/es not_active Expired - Lifetime
- 1994-08-16 DE DE69430611T patent/DE69430611T2/de not_active Expired - Fee Related
- 1994-08-16 EP EP94112803A patent/EP0639577B1/en not_active Expired - Lifetime
- 1994-08-16 DK DK94112803T patent/DK0639577T3/da active
- 1994-08-16 PL PL94304649A patent/PL179636B1/pl not_active IP Right Cessation
- 1994-08-16 PT PT94112803T patent/PT639577E/pt unknown
-
1998
- 1998-11-06 AU AU91356/98A patent/AU706511B2/en not_active Ceased
-
1999
- 1999-02-08 IL IL12842599A patent/IL128425A0/xx unknown
- 1999-04-29 CN CN99105343A patent/CN1100771C/zh not_active Expired - Fee Related
-
2002
- 2002-09-05 CY CY0200054A patent/CY2295B1/xx unknown
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